A team of researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine recently received Department of Defense Breast Cancer Research Program awards to study new therapeutic targets based on the genomic changes that drive tumor formation.

The two awards for the partnering principle investigators total $781,455; and were given to BCM young investigator Dr. Xiaosong Wang, assistant professor in the Smith Breast Center, and Dr. Rachel Schiff, associate professor in the Smith Breast Center.

Wang is trained in bioinformatics, genomics, molecular biology and gene fusion research with four years prior experience as a surgeon. Schiff is an established scientist in breast cancer biology, molecular therapeutics, drug resistance and in vivo therapeutic models.

'Haystack' of genetic changes

"We know that some of the most successful cancer therapeutics target genetic aberrations, such as gene fusions and gene amplifications," said Wang.

Gene fusion occurs when chromosomes translocate and fuse together pieces of two different genes. Gene amplification occurs when there is repeated copying of a gene sequence.

'Driver' gene fusions and amplifications are keys for tumor progression and successful targeted therapies; however, the cancer genome usually harbors a large amount of non-specific changes as well.

"If you sequence a breast cancer tumor, you will typically find a 'haystack' of these changes. So the challenge is how to identify what are the drivers of the changes and target them directly," said Wang.

Digital "eagle eye"

Using publicly available datasets, Wang and his team will use a novel bioinformatics tool – which Wang developed – to analyze the intensive amount of data produced from a human tumor genome sequence and identify the operations of these genetic changes.

"Using computational technology, we will zoom into the genome to identify the key changes that control the cancer cells," said Wang.

"The new technology can substantially improve and advance the interpretation of these data, incorporating significant new data sets immediately reanalyzing and updating", she said.

Benefits

The drivers, Wang said, serve as attractive drug targets. Some of the targets may already be developed into therapeutics for other diseases and could be more rapidly available to study in breast cancer, Wang said. Other targets could lead to new drug development.

"At BCM, we have established a unique Cancer Genetics Laboratory," said Schiff. "We envision that down the road, these new targets could be translated into diagnostic assays as well that will be developed by the laboratory."